Contraceptive efficacy and safety studies of a novel microemulsion-based lipophilic vaginal spermicide

Abstract

Objective: To investigate the in vivo contraceptive potency and safety of a novel microemulsion-based lipophilic vaginal spermicide. Design: In vitro and in vivo spermicidal activity and safety of a submicron-particle-size, lipophilic gel–microemulsion (GM-4). Setting: Center for Advanced Preclinical Sciences at the Parker Hughes Institute. Patient(s): Nine male volunteer sperm donors. Intervention(s): Motile human sperm in semen and medium were exposed to eight GM-4 components or GM-4 formulation. Forty-eight ovulated NZW rabbits in subgroups of 16 with or without intravaginal administration of GM-4 or nonoxynol-9 gel (N-9; Gynol II) were artificially inseminated and allowed to complete pregnancy. Eleven rabbits were exposed to daily intravaginal application of GM-4 with and without N-9 for 10 consecutive days. Ten of 20 B 6C 3F 1 mice were given repetitive intravaginal application of GM-4 for 5 days/week over 13 consecutive weeks. Main Outcome Measure(s): The motility of human sperm treated with GM-4 components and GM-4. Term pregnancy in rabbits and histopathological grading of rabbit vaginal tissue for irritation. Evaluation of mice for survival, growth, hematologic parameters, blood-chemistry profiles, absolute and relative organ weights, and histopathology. Result(s): The individual components of GM-4 lacked spermicidal activity in human semen, whereas the GM-4 formulation containing all the eight pharmacological excipients exhibited potent spermicidal activity with rapid kinetics. GM-4 showed remarkable contraceptive activity in the rigorous rabbit model. None of the 16 (0%) rabbits given GM-4 intravaginally before artificial insemination became pregnant. By contrast, 15 of 16 (93.7%) control rabbits and 5 of 16 (31.2%) Gynol II-treated rabbits became pregnant and delivered newborns. Thus, GM-4 was a significantly more effective contraceptive than a commercially available N-9 gel [100% vs. 68.7% protection; P< 0.05, Fisher’s exact test]. Unlike the rabbits treated with N-9, none of the rabbits that were given GM-4 intravaginally for 10 consecutive days developed epithelial ulceration, edema, leukocyte influx, or vascular congestion characteristic of inflammation. Furthermore, repeated intravaginal application of GM-4 for up to 13 weeks in mice had no adverse effects on survival, growth, metabolism, or organ function. Conclusion: We conclude that the novel spermicidal GM-4 formulation is safe and significantly more effective than N-9 in preventing conception.